Gut microbiota-derived trimethylamine-N-oxide inhibits SIRT1 to regulate SM22α-mediated smooth muscle cell inflammation and promote atherosclerosis progression

IF 3.6 3区 生物学 Q3 CELL BIOLOGY
Yajuan Yin, Mei Wei, Xiufang Jiang, Mei Liu, Xiaocui Shi, Xiao Zhang, Le Wang, Gang Liu, Mingqi Zheng, Fangfang Ma
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Abstract

Atherosclerosis (AS) is a prevalent cardiovascular disease, and emerging evidence highlights the critical role of gut microbiota in its development. Trimethylamine-N-oxide (TMAO), a metabolite derived from gut microbiota, is thought to promote AS progression by regulating smooth muscle protein 22-alpha (SM22α)-mediated inflammation in vascular smooth muscle cells. This study aims to explore the molecular mechanisms of TMAO in AS through multi-omics analysis, particularly its effects on SIRT1 inhibition and SM22α modulation. 16S ribosomal RNA sequencing revealed an altered gut microbiota composition in AS mice, characterized by increased Bacteroides and decreased Firmicutes. Metabolomics analysis indicated elevated levels of TMAO in AS mice. Transcriptomic data and cell experiments further confirmed that TMAO promotes AS by regulating SM22α-mediated inflammation via SIRT1 regulation. These findings suggest that TMAO accelerates progression through the SIRT1 and SM22α-related pathways, offering novel therapeutic targets for AS intervention.

Abstract Image

肠道微生物源性三甲胺- n -氧化物抑制SIRT1调节sm22 α介导的平滑肌细胞炎症,促进动脉粥样硬化进展
动脉粥样硬化(AS)是一种常见的心血管疾病,新出现的证据强调了肠道微生物群在其发展中的关键作用。三甲胺- n -氧化物(TMAO)是一种来自肠道微生物群的代谢物,被认为通过调节血管平滑肌细胞中平滑肌蛋白22- α (SM22α)介导的炎症来促进AS的进展。本研究旨在通过多组学分析探讨TMAO在AS中的分子机制,特别是其对SIRT1抑制和SM22α调节的影响。16S核糖体RNA测序显示AS小鼠肠道菌群组成发生改变,其特征是拟杆菌增加,厚壁菌门减少。代谢组学分析表明,AS小鼠的TMAO水平升高。转录组学数据和细胞实验进一步证实,TMAO通过SIRT1调控sm22 α介导的炎症,从而促进AS的发生。这些发现表明,TMAO通过SIRT1和sm22 α相关途径加速进展,为AS干预提供了新的治疗靶点。
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来源期刊
CiteScore
6.40
自引率
4.90%
发文量
40
期刊介绍: The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.
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